Our overall goal is to continue our analysis of how regulatory proteins recognize specific sequences in DNA and turn transcription of genes on and off. We will continue to use biochemical, genetic, and physical methods for studying the structures and interactions of the protein and DNA molecules. We will concentrate on phage lambda and related organisms; the study of phage lambda has provided us with our most precise understanding of these processes, and recent developments promise important extensions of our understanding. Building in part on the results of X-ray crystallography, we now have precise models for how a large class of regulatory proteins recognize specific sequences in DNA, and aspects of these models will be further tested. The action of lambda repressor as a positive regulator provides a model for gene activation, and we will further explore the protein-protein interactions that underlie that process. The remarkable ability of lambda repressors to bind cooperatively to sites widely separated on DNA, with concomitant DNA looping, provides a suggestion of how many apparently disparate forms of gene activation and repression may by manifested by a common underlying mechanism; we will explore this important cooperative interaction in vivo and in vitro and study its effect on gene regulation.